This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. Natural Killer T(NKT) lymphocytes are a unique subset of T lymphocytes that have an invariant TCR Valpha chain and recognize ligands presented by the nonpolymorphic CD1d molecule. They are early effectors of the innate immune system, and can secrete large amounts of both Th-1 and Th-2 type cytokines, including IL-10 that may play a role in modulating immune activation in HIV and SIV infection. Sooty mangabeys are a natural host of SIV that is non-progressive;key differentiating feature of this SIV infection is the absence of aberrant immune activation. .In this investigation we hope to determine if NKT cells in naturally SIV-infected sooty mangabeys are responsible for this absence of aberrant immune activation. .Flow cytometric evaluation of peripheral blood in 50 SIV negative and 50 SIV positive sooty mangabeys has revealed detectable frequencies of circulating Valpha 24positive CDld NKT lymphocytes in approximately 50% of sooty mangabeys. Comparison of NKT lymphocytes in natural and non-natural hosts of SIV infection is in progress.